This grant supports research into two area: fetal opiate dependence and withdrawl, and the placental transfer of opiates. Studies are performed on chronically catheterized pregnant ewes. Opiate dependence is produced by long-term infusions of morphine into the mother and abrupt discontinuation of morphine administration produces abrupt withdrawal in the mother and fetus. Physiologic responses in both are measured. The specific effects of maternal withdrawal on fetus will be studied by the simultaneous infusions of morphine into the mother and naloxone into the fetus. This should lock the development of dependence in the fetus. Placental transfer and maternal and fetal elimination of morphine are being studied in the pregnant ewe. Initial studies indicate that when morphine is infused into the mother, the intrinsic rate of loss of drug from the mother is 98% of the infusion rate and 2% is lost to the placenta and fetus. When morphine is infused into the fetus, the intrinsic rate of loss of drug from the fetus is 75% of the infusion rate, and 25% is lost to the placenta and mother. This indicates that the fetus is responsible for eliminating a major amount of drug which enters the general fetal circulation.